User:Lisa1235858/Versutoxin

From Wikipedia, the free encyclopedia
Delta Atracotoxin Hv1a
3D stick model of delta-atracotoxin-Hv1 (versutoxin)
Identifiers
SymbolAtracotoxin Hv1
PfamPF05353
InterProIPR008017
OPM superfamily112
OPM protein1vtx
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Article Draft[edit]

Delta atracotoxin Hv1 (δ-ACTX-Hv1a, Versutoxin, or Versutotoxin) is a neurotoxic component found in the venom of the Australian funnel web spider (Atrax robustus).

Delta atracotoxin Hv1 can result in fatality in primates by downregulating the inactivation of voltage gated sodium ion channels found in motor neurons.

The structure of versutoxin contains a central beta region with a inhibitor cystine knot (ICK), commonly found in other neurotoxic polypeptides, but not found in sea anemone or alpha-scorpion toxins despite their similar effects in terms of sodium channel modulation.[1][2]

Nomenclature[edit]

In 1997, Jamie I. Fletcher and his research associates introduced new nomenclature for classifying Australian funnel web spider toxins. They suggested replacing the trivial name 'versutoxin' with delta-atracotoxin-Hv1 instead. The delta represents the main biological activity of the neurotoxin; inhibiting sodium channels.[1][3]

History[edit]

Although over 40 different species of funnel web spiders are known, the male Atrax robustus is known to have the most human fatalities, prior to the introduction of antivenom in 1981.[4][5]

Structure[edit]

Delta atracotoxin Hv1 is a tightly folded polypeptide that contains a chain of 42 animo acid residues and has the chemical formula C206H318N58O60S9. [6] The animo acid sequence of delta atracotoxin Hv1 is:

C A K K R N W C G K T E D C C C P M K C V Y A W Y N E Q G S C Q S T I S A L W K K C

Three Dimensional Structure[edit]

The tertiary structure of δ-ACTX-Hv1 contains a core β region that is made up of the residues Cys1Cys8, Cys14Val21, and Ser30Ser33, with Tyr22Gly29 protruding outwards. The β region has a three-stranded antiparallel β sheet comprising Asn6–Trp7 (β1), Met18–Val21 (β2), and Ser30–Ser33 (β3). The C-terminal end of the short β1 is held in place by a bifurcated hydrogen bond between the Cys8 amide proton and the carbonyl oxygens of the two residues preceding β strand 3 (Gln28 and Gly29). The β region also contains type II β turns at Lys3–Asn6 and Cys15–Met18 with a rare cis peptide bond at Cys16–Met 17. The nonpolar C-terminal 310 helix formed by Ile35Lys41, bordering Lys40 and Lys41 and connecting to β region with a disulphide bond next to a β turn. The β region contains hydrophobic cysteine sidechains bordered by a lysine sidechain.Three of the four disulphide bonds form the ICK.[3]

Toxicity[edit]

See Also[edit]

References[edit]

  1. ^ a b Fletcher, Jamie I; Chapman, Bogdan E; Mackay, Joel P; Howden, Merlin EH; King, Glenn F (November 1997). "The structure of versutoxin (δ-atracotoxin-Hv1) provides insights into the binding of site 3 neurotoxins to the voltage-gated sodium channel". Structure. 5 (11): 1525–1535. doi:10.1016/S0969-2126(97)00301-8.
  2. ^ Lüddecke, Tim; Herzig, Volker; Reumont, Björn M. von; Vilcinskas, Andreas (August 2021). "The biology and evolution of spider venoms". Biological Reviews. n/a (n/a). doi:10.1111/brv.12793. ISSN 1469-185X.
  3. ^ a b Fletcher, Jamie I.; Smith, Ross; O'Donoghue, Séan I.; Nilges, Michael; Connor, Mark; Howden, Merlin E. H.; Christie, Macdonald J.; King, Glenn F. (July 1997). "The structure of a novel insecticidal neurotoxin, ω-atracotoxin-HV1, from the venom of an Australian funnel web spider". Nature Structural Biology. 4 (7): 559–566. doi:10.1038/nsb0797-559. ISSN 1545-9985.
  4. ^ Binstead, Justin T.; Nappe, Thomas M. (2021), "Funnel Web Spider Toxicity", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30571015, retrieved 2021-11-11
  5. ^ Isbister, Geoffrey K.; Gray, Michael R.; Balit, Corrine R.; Raven, Robert J.; Stokes, Barrie J.; Porges, Kate; Tankel, Alan S.; Turner, Elizabeth; White, Julian; Fisher, Malcolm McD (2005-04-18). "Funnel-web spider bite: a systematic review of recorded clinical cases". Medical Journal of Australia. 182 (8). ISSN 0025-729X.
  6. ^ Brown, M R; Sheumack, D D; Tyler, M I; Howden, M E (1988-03-01). "Amino acid sequence of versutoxin, a lethal neurotoxin from the venom of the funnel-web spider Atrax versutus". Biochemical Journal. 250 (2): 401–405. ISSN 0264-6021. PMC 1148870. PMID 3355530.

Category:Neurotoxins